The aim of our studies is to understand the factors regulating lipogenesis and gluconeogenesis in mammalian tissues. During the past year we have concentrated on the hormonal regulation of the enzyme P-enolpyruvate carboxykinase of mammalian liver. We have shown that the synthesis rate of this enzyme, as measured with immunochemical techniques, is decreased from 3 percent to approximately 0.2 percent by refeeding starved animals. The half time of this rate of decline in the synthesis of P-enolpyruvate carboxykinase is 30 minutes. A similar fall in the rate of enzyme synthesis was noted when insulin was injected into diabetic animals. The half time of template mRNA for P-enolpyruvate carboxykinase as estimated by the use of the inhibitor cordycepin is 40 minutes; this applies to animals that are starved and refed or starved. Preliminary studies have indicated that the site 1 inhibitor cycloheximide can act to decrease the rate of lipid metabolism in isolated rat epididymal adipose tissue. This inhibition has been associated with the role of ATP in regulating the rates of lipogenesis in adipose tissue. We have also shown that guinea pig liver does not carry out fatty acid synthesis to an appreciable extent. This in contrast to the liver of fetal guinea pigs which has the capacity to synthesize fatty acids from glucose before birth. These studies indicate a fundamental difference between species in the regulation of hepatic fatty acid synthesis.